The magic of iPSCs
IPSCs are created when a normal adult cell is reprogrammed to become ‘pluripotent’, meaning it is able to give rise to all the different kinds of cells that make up the human body. As such, human iPSCs can provide scientists with a variety of human cell types that can be used in research and drug development. Research tools based on human iPSCs offer the promise of more reliable results than research tools based on animal cells. When StemBANCC started, iPSC technology was still in its infancy and many scientists struggled to access high quality, well-characterised human iPSCs for use in research.
The goal of StemBANCC was to make a large number of iPSC lines available for the scientific community. The cells came from people with neurodysfunctional diseases (migraine, autism, schizophrenia, and bipolar disorder), central nervous system disorders (dementias), peripheral nervous system disorders (pain), and diabetes, as well as people who had experienced adverse reactions to drugs and healthy people. By the end of the five-year project, the team had generated 491 quality controlled, well-characterised iPSC lines from 496 people. In this way, StemBANCC addressed the challenge of finding more reliable ways to translate results from early laboratory tests to human patients. The iPSC lines are now accessible to the scientific community through EBiSC and Coriell.
Rigid ethical standards
Another important project outcome is the strict quality control and traceability of the iPSCs. Biological material (e.g. blood and skin samples), was collected from the recruited patients and healthy individuals with their informed consent and in line with rigid ethical standards. As an example of the practical traceability system, StemBANCC has met scientific, ethical and legal requirements to protect donor privacy while also maximising the availability of data. The system tracks samples throughout reprogramming and across the various physical locations where processing occurs within the StemBANCC consortium.
Other important project achievements include:
- new standardised protocols to generate different types of nerve cells from iPSCs; the protocols have been reproduced in multiple labs, proving their robustness;
- therapeutically relevant disease models in pain and Parkinson’s disease;
- new data on disease phenotypes including pain disorders, Alzheimer’s disease, Parkinson’s disease, autism, and diabetes;
- a study on the effect of drugs on a range of iPSC derived cell types, providing researchers with an important source for future work;
- the creation of the single-point access database (operated by StemDB) with all relevant iPSC information.
For the benefit of industry, academia, and SMEs
Thanks to StemBANCC, the scientific community now has high quality, disease-relevant human iPSCs already that are already being used to study disease biology, and to discover and develop new drugs.
Through StemBANC, there has been a significant transfer of knowledge from industry to academia and SMEs on how to use iPSCs to establish disease models for translational research. Furthermore, academia obtained a deeper understanding of the critical requirements of turning basic biomedical research into medicines, while undertaking the joint projects that are globally unique, which resulted with the utilisation of complementary expertise and knowledge in academia and industry. Academics also gained best practice on working with iPSC disease models to ensure reproducibility of the results.
For their part, the pharmaceutical companies involved in the project have used StemBANCC to establish their own stem cells expertise, and they are now using relevant in vitro models and assays in early stage drug discovery and safety evaluation.
SME Newcells Biotech is a spin-out company from the University of Newcastle, that is producing, reprograming and differentiating iPSC lines and creating innovative cross-species tests for specific studies. Another spin-off combines the analysis of electronic health records with stem cell studies in order to validate the data.
The accessibility of iPSC lines with the donors’ disease background and the development of the disease-relevant cell types could lead pharmaceutical companies to make further investments as a means of increasing the chances of translating drug candidates into efficacious treatments for the patients. The work of StemBANCC has significantly contributed to establishing methods and platforms to de-risk drug discovery. Ultimately, the use of human cellular models will enable improvements in the selection of compounds that are efficacious and reduce the risk of toxicity. Although these benefits will take some time to materialise, StemBANCC has laid the foundations. Additionally, the generation of relevant cells and assays can in the future potentially lead to a reduction in the use of animals in drug development, thus providing one more important legacy for StemBANCC.
Achievements & News
One of the biggest challenges in drug development is finding ways to translate results from early laboratory tests to human patients. Pluripotent stem cells derived from human patients might hold the key to this translational puzzle, and a new IMI study confirms this potential.### In a unique collaboration, both IMI’s EBiSC and StemBANCC project teams contributed to a study led by one of their industrial project partners, Pfizer. The study set out to improve the understanding of a rare pain disease called inherited erythromelalgia (IEM). IEM is a chronic condition with no adequate medical treatment, in which patients suffer from extreme pain that is made worse by heat. The disease is caused by a mutation in a gene leading to overactivity of a sodium channel in patients’ sensory neurons. Pfizer scientists examined if a new experimental drug could block this sodium channel and reduce the pain experienced by IEM patients. When tested on five patients, results indicated that the drug reduced pain upon exposure to heat in most sufferers. However, the experiment didn’t end there. The same patients allowed scientists to take their blood cells and transform them into pluripotent stem cells, which were deposited in the EBiSC project stem cell bank. Next, the StemBANCC scientists turned some of those stem cells into sensory neurons and studied their characteristics in a lab. Prior to treatment, the neurons showed hyper-excitability and an unusual response to heat: the more severe the disease was in a patient, the more the neurons became hyper-excited. When the same neurons were treated with the experimental drug, the hyper-excitability diminished, mimicking the drug effect that occurred in patients. 'This is an exciting study,' said Andrea Weston, Pfizer’s scientific lead for StemBANCC and EBiSC projects. 'Rarely is it possible for drug developers to be able to study the drug responses of the actual, relevant cells from individual patients who are involved in clinical trials of the same experimental drug. These results illustrate that stem cell technology has the potential to transform the way in which drugs are made, enabling scientists to make them much more precise and tailored to individual patients. This is also a good example of how technology can bridge the translational gap between preclinical models and clinical evaluation. The study was facilitated by the collaborative nature of IMI’s projects, and wouldn’t have been possible without the open exchange of knowledge and ideas between different project partners.’
IMI’s stem cell project StemBANCC is advancing well with the recruitment of patients and control individuals (subjects). So far, around 50 subjects have been recruited to disease cohorts such as Alzheimer’s disease, neuropathy, diabetes, Parkinson’s disease, migraine and bipolar disorder by several project participants.### The sites recruiting for the autism and schizophrenia cohorts expect to have their first patients in soon.
StemBANCC aims to generate and characterise 1 500 high quality human induced pluripotent stem (iPS) cell lines from 500 people that can be used by researchers to study a range of diseases and test for drug efficacy and safety. The raw materials for the project are largely skin samples taken from patients with certain diseases, people who display adverse reactions to drugs, and healthy individuals. The collection of these samples is carried out with the individuals’ informed consent and in line with strict ethical standards.
The recruitment of subjects began following the full ethics approval by the UK’s main research ethics committee in 2013. The University of Oxford, which is also the managing entity of the StemBANCC project, is responsible for recruiting more than half of the required target of 500 patient and healthy volunteers.
- Learn more about the StemBANCC project
ParticipantsShow participants on map
- Abbvie Deutschland GMBH & Co Kg, Wiesbaden, Germany
- Astrazeneca AB, Södertälje, Sweden
- Boehringer Ingelheim Internationalgmbh, Ingelheim, Germany
- Eli Lilly And Company LTD, Basingstoke, United Kingdom
- F. Hoffmann-La Roche AG, Basel, Switzerland
- Janssen Pharmaceutica Nv, Beerse, Belgium
- Merck Kommanditgesellschaft Auf Aktien, Darmstadt, Germany
- Novo Nordisk A/S, Bagsvaerd, Denmark
- Orion Oyj, Espoo, Finland
- Pfizer Limited, Sandwich, Kent , United Kingdom
- Sanofi-Aventis Recherche & Developpement, Chilly Mazarin, France
Universities, research organisations, public bodies, non-profit groups
- Charite - Universitaetsmedizin Berlin, Berlin, Germany
- Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Fuer Gesundheit Und Umwelt GMBH, Neuherberg, Germany
- Institut National De L Environnement Industriel Et Des Risques - Ineris, Verneuil En Halatte, France
- Institut National De La Sante Et De La Recherche Medicale, Paris, France
- King'S College London, London, United Kingdom
- Linkopings Universitet, Linkoping, Sweden
- Medizinische Hochschule Hannover, Hannover, Germany
- Medizinische Universitat Innsbruck, Innsbruck, Austria
- Naturwissenschaftliches Und Medizinisches Institut An Der Universitaet Tuebingen, Reutlingen, Germany
- Region Hovedstaden, Hilleroed, Denmark
- Tel Aviv University, Tel Aviv, Israel
- The Hebrew University Of Jerusalem, Jerusalem, Israel
- The University Of Birmingham, Birmingham, United Kingdom
- The University Of Edinburgh, Edinburgh, United Kingdom
- UNIVERSITAET zu LUEBECK, Luebeck, Germany
- Universite De Geneve, Genève 4, Switzerland
- Universite De Lausanne, Lausanne, Switzerland
- Universite De Technologie De Compiegne, Compiegne, France
- University College London, London, United Kingdom
- University Of Newcastle Upon Tyne, Newcastle upon Tyne, United Kingdom
- University of Cambridge, Cambridge, United Kingdom
- University of Oxford, Oxford, United Kingdom
Small and medium-sized enterprises (SMEs)
- Concentris Research Management GMBH, Fürstenfeldbruck, Germany
- Human Cell Design, Toulouse, France
- Newcells Biotech Limited, Newcastle upon Tyne, United Kingdom
- Universitatsklinikum Schleswig-Holstein, Lübeck, Germany
|Name||IHI funding in €|
|Charite - Universitaetsmedizin Berlin||383 476|
|Concentris Research Management GMBH||623 147|
|Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Fuer Gesundheit Und Umwelt GMBH||758 325|
|Human Cell Design||783 535|
|Institut National De L Environnement Industriel Et Des Risques - Ineris||132 600|
|Institut National De La Sante Et De La Recherche Medicale||1 006 625|
|King'S College London||1 080 474|
|Linkopings Universitet||460 172|
|Medical Research Council (left the project)||32 111|
|Medizinische Hochschule Hannover||819 681|
|Medizinische Universitat Innsbruck||383 476|
|Naturwissenschaftliches Und Medizinisches Institut An Der Universitaet Tuebingen||881 996|
|Newcells Biotech Limited||140 987|
|Region Hovedstaden||167 771|
|Tel Aviv University||431 411|
|The Hebrew University Of Jerusalem||431 411|
|The University Of Birmingham||175 284|
|The University Of Edinburgh||1 921 723|
|UNIVERSITAET zu LUEBECK||63 337|
|Universite De Geneve||575 214|
|Universite De Lausanne||383 476|
|Universite De Technologie De Compiegne||250 877|
|University College London||1 462 000|
|University of Cambridge||958 690|
|University Of Newcastle Upon Tyne||1 886 399|
|University of Oxford||9 099 682|
|Name||Funding in €|
|Universitatsklinikum Schleswig-Holstein||706 120|
|Total Cost||26 000 000|